A 42-year-old woman presented to our institution with a 2-week history of bone pain in the lower extremities. Her history was remarkable for duodenal ulcer and long-term treatment with a magnesium-aluminum hydroxide antacid (Maalox) and sucralfate. Initial laboratory studies showed severe hypophosphatemia and elevated alkaline phosphatase and serum 1,25-dihydroxyvitamin D levels. Bone scan showed multiple areas of increased uptake consistent with osteomalacia and microfractures. The patient recovered completely following withdrawal of antacids and sucralfate and short-term treatment with phosphate. Although hypophosphatemia induced by aluminum-containing antacids is rare, treatment of peptic ulcer disease with a combination of two aluminum-containing agents may increase the risk of clinically significant hypophosphatemia. Awareness of this condition is important, because early recognition can prevent morbidity and lead to safe and effective treatment.